Earticle

Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, has increased in cancer patients and adversely affects their prognosis. Low-molecular-weight heparins are recommended as efficacious and safe anticoagulation treatment in cancer patients. However, in practice, oral anticoagulation is preferred, especially if longterm or extended treatment is necessary. Novel oral anticoagulants have recently emerged as an alternative to the standard therapy owing to the ease of administration, predictable anticoagulation effect without the need of laboratory monitoring, and fewer drug interactions. These new agents have been shown as effective and safe for the management of cancer- associated thrombosis in ongoing head-to-head comparative trials. Here we review the advances and limitation of current anticoagulant therapies.

Experiential education is a core curriculum of 6-year pharmacy education. Practicing pharmacists lie at the heart of experiential education serving as preceptors for undergraduate pharmacy students during experiential education. Preceptors are, however, confronted with a challenge of caring for patients and teaching students at the same time in a time-constrained environment. To improve the effectiveness and outcomes of experiential education, practicing pharmacists are required to demonstrate educational competence. Even small teaching moments can provide students with valuable learning opportunities that they could not have from on their own. Thus, it is vital to provide education and training for preceptors to advance their teaching skills. This article will describe practical and effective teaching skills that preceptors could adopt in the experiential education for pharmacy students. It is important that preceptors should use different teaching skills for different learners, according to their level of experience and knowledge, learning styles and needs, as well as the type of the practice. Therefore, possessing diverse teaching skills provides flexibility to adapt teaching to each student's learning levels and needs, and to the charateristics of the practice environment. Preceptors' level of confidence and comfort in using teaching skills can be enhanced through continuous practice and training, which consequently leads to the improved effectiveness of experiential education and student's satisfaction with the education.

Background: The current educational goals and missions of pharmacy schools in Korea were analyzed to examine the current orientation and future direction of pharmaceutical education. Methods: Educational mission statements were obtained from the homepages of 35 pharmacy schools and subjected to convert into codes. Themes and categories were induced using qualitative content-analysis from the codes and compared according to location of school (capital area versus province), public versus private, and date of initial enrollment (before versus in 2011). The themes and categories were compared with "the eight-star pharmacist" suggested by World Health Organization (WHO) and International Pharmaceutical Federation (FIP). Results: Twelve themes, 44 categories, and 496 codes were identified. Themes included pharmaceutical expertise, professionalism, contribution to society, basic educational ideology, sphere of activity, leadership, research, dealing with future change, problem-solving ability, self-management and development, cooperation, and respect for life. Mission statements of schools that initially enrolled in 2011 cited humankind level contribution (p=0.011), patient-centered care (p=0.026), and globalization (p=0.018) more frequently than those enrolled before 2011. Most schools mentioned about care-giver, researcher, and decision-maker which were stated in "the eight-star pharmacist". Conclusion: To meet the growing social requirements of a pharmacist's roles, wide-ranging active discussion on establishing educational goals should be made.

Background: This study is to investigate the prescription patterns and factors related to the number of medications treating chronic obstructive pulmonary disease (COPD) in patients under 65 years old according to GOLD guidelines. Methods: We retrospectively analyzed the medical records of patients aged 40-64 years with a diagnosis of COPD from January to March 2016. Patients were classified by combined assessment of COPD (grades A, B, C, D) using spirometry, exacerbation history, mMRC, and/or CAT results. We analyzed prescribed medications, treatment options and factors related to the numbers of COPD medications. Results: The total number of prescriptions were 251. About 35.5% of patients were classified as GOLD A, 34.2% as GOLD B, 17.1% as GOLD C and 13.2% as GOLD D. Inhaled bronchodilator was prescribed for 86.9% of patients and the most frequent COPD medication was longacting muscarinic antagonist (LAMA) followed by inhaled corticosteroids/long acting beta agonist (ICS/LABA). The majority of low risk patients (GOLD A/B) were prescribed a monotherapy with LAMA or LABA. For high risk patients (GOLD C/D), combination treatment with ICS+LAMA+LABA was mostly prescribed. The 21.2% of patients in GOLD D received systemic corticosteroid. The average number of medications per prescription was 3.7, and this number increased with increasing COPD grade, COPD duration and lung function reduction (FEV1, FEV1/FVC). Conclusion: Generally high adherence to GOLD guideline recommendations was reported. Given the progressive nature of the disease, results suggest that closer attention to respiratory symptoms for early detection, diagnosis, and appropriate treatment of COPD is warranted.

Objective: This study was performed to compare the changes in the blood concentrations of tacrolimus when either itraconazole or voriconazole is together with tacrolimus to prevent or treat invasive aspergillus pneumonia (IAP) in patients with lung transplants. Therefore we can compare the degree of drug-drug interactions between tacrolimus and itraconazole against tacrolimus and voriconazole. Methods: Patients who were admitted and had lung transplants in a territory referral hospital from September 2012 to May 2015 were analyzed retrospectively. The effects of itraconazole and voriconazole on the plasma concentrations of tacrolimus were analyzed. Results: Mean tacrolimus concentrations was 10.49±2.35 ng/mL vs. 10.95±2.98 ng/mL (p=0.722), and mean concentration of tacrolimus over the dose of tacrolimus per day was 8.510±5.890 (ng/mL)/(mg/d) vs. 15.45±28.47 (ng/mL)/(mg/d) (p=0.947) in itraconazole vs. voriconazole group each. The ratio of the number of the results out of target tacrolimus concentrations to the total number of tacrolimus concentration results was 18.0±13.3% vs. 24.4±18.5% (p=0.185). Conclusion: There were no significant differences between itraconzaole and voriconazole to have influences on mean concentrations of tacrolimus over tacrolimus dose per weight per day. However voriconazole tended to raise tacrolimus plasma concentrations more than itraconazole. Safer and more effective drug management to prevent and treat fungal infections should be done by therapeutic drug monitoring not only of tacrolimus but of itraconazole and voriconazole in lung transplant patients.

Objective: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. Methods: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model (NONMEM® 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. Results: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. Conclusion: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.

Background: Multidisciplinary team care (MTC) is a collaborative approach to treatment plan and ongoing care. We aimed to evaluate the clinical effect of MTC on the regulation of chronic kidney disease-mineral and bone disorder (CKD-MBD) complications in dialysis patients. Methods: This retrospective observational study was approved by the institutional review board. Among patients who have undergone dialysis at admission, the patients admitted to the nephrology ward were allocated to MTC group, and the others to usual care (UC) group. The MTC group had collaborative care by nephrologists, nurses, pharmacists, and nutritionists. The endpoints were the regulation of corrected calcium (cCa) and phosphate (P), the percent of patients in target level of cCa-P product (cCa×P), and the prescription rate of non-calcium based P-binders. Results: A total of 163 patients were included from January to December 2009. A significant difference was shown in the percentage of patients in target cCa×P level at admission (MTC vs. UC, 81.40% vs. 91.67%; P = 0.038), but there was no significant difference at discharge. During admission, the cCa and P levels of patients in only UC group were significantly changed. In addition, compared with UC group, patients in MTC group were more likely prescribed appropriate P-binders, when they had higher cCa×P levels than 55 mg2/dL2 (P <0.001). Conclusion: It was found that MTC had beneficial effect on improving the regulation of CKD-MBD and the appropriate phosphate binder uses. Therefore, application of the MTC is anticipated to enhance quality of clinical care in chronic diseases.

Background: With the development of information and communication technology, there is a growing number of people looking for health information on the internet. This pilot study was performed to analyze the pattern of pharmacist consultation on the internet portal site. Methods: Questions and answers posted on the portal site "Naver Jisik-iN" from March 1st to 31th in 2016 were collected. Medications asked were categorized into prescription drugs, nonprescription drugs, sanitary aids, emergency drugs, functional health foods, and others. Medications were subcategorized into 14 according to the anatomical therapeutic chemical classification system. Questions were divided into 10 categories based on Hepler's drug-related problems. Results: Of the 955 cases, females accounted for 59.5% and inquirers from 11 to 40 years old, 89.4%. The number of prescription drugs, nonprescription drugs, sanitary aids, emergency drugs, functional health foods, and others were 428 (44.8%), 328 (34.3%), 31 (3.3%), 2 (0.2%), 122 (12.8%), and 44 (4.6%), respectively. Questions for drugs acting on alimentary tract and metabolism took up 27.4% followed by those on nervous system, 13.6% and anti-infectives for systemic use, 12.2%. Pharmacist consultation regarding drug information, drug interaction, and adverse reaction occupied 47.9%, 15.2%, and 12.3%, respectively. Conclusion: Health counseling through online is predicted to increase steadily, so pharmacists should broaden their boundaries beyond off-line pharmacies to meet social needs.

Objective: The outbreak of Middle East Respiratory Syndrome (MERS) started in South Korea in May 2015 and the end of crisis was declared in December 2015 by Korea Centers of Disease Control and Prevention (KCDC). However, Zika virus emerged in less than 2 months following MERS and showed higher mortality than other countries. This study is to assess the current prevention system of overseas infectious diseases, based on MERS and Zika virus outbreak and to suggest effective response system for the future. Methods: We conducted two surveys on medical specialists working at tertiary general hospitals regarding the effectiveness of responding system by KCDC against MERS and Zika virus and education in individual medical institutions using 5-Likert points. Response system was examined in three different periods as initial period, spreading period, and post disease period. Results: Although medical specialists received the notifications in initial period, no practical prevention was proven to be placed in responding stage by medical facilities (averagely 3.5/5 points in total and sub-analyses). During spreading period, there were several academic seminars conducted, which were evaluated as helpful. In post disease period, all answered that there were changes on patient treatment in all medical facilities, with mainly report system and the treatment regulations in case of suspicious patients for infection. Only 49% respondents answered positive on the possibility of initial responses. For questionnaire items regarding Zika virus, all answered that there were notifications prior to the first outbreak of the infected patient. Eighty% of respondents were aware of 'the Guideline system for traveling to dangerous areas', and answered that the system was moderately effective (averagely 3.8/5 points in total). For the effectiveness of prevention measures for foreign novel disease by KCDC, the average point was 3.0 in both of total and sub-analyses. Conclusion: There is not enough response system to prevent infectious disease in medical institutional and governmental levels in Korea. It would warrant the modification of overall medical system to improve preventive measures for initial spread of such diseases.

Background: Liver cirrhosis causes substantial socio-economic burden and is one of the major severe liver diseases in Korea. Nonetheless, there is only a few studies that analyzes disease burden of liver cirrhosis in Korea. Such study must be carried out due to its increasing need from the invention of new drugs for chronic hepatitis and demand for cost-effectiveness analyses. Methods: Patient sample data with ensured representativeness was analyzed retrospectively to compare the medical costs and uses for patients with compensated cirrhosis and decompensated cirrhosis. Patient claims data that include K74 and K703 from the year of 2014 were selected. Within the selected data, decompensated cirrhosis patient was identified if complications such as ascites (R18), encephalopathy (B190), hepatic failure (K72), peritonitis (K65), or esophageal varices (I85) were included, and they were compared to compensated cirrhosis patients. Results: 6,565 patients were included in the analysis. The average cost per patient was 6,471,020 (SD 8,848,899) KRW and 2,173,203 (4,220,942) KRW for decompensated cirrhosis and compensated cirrhosis, respectively. For inpatients, the average hospitalized days was 38.0 (56.4) days and 27.2 (57.2) days for decompensated cirrhosis and compensated cirrhosis, respectively. For outpatients, the average number of visits was 8.7 (9.1) days and 5.3 (7.5) days for compensated cirrhosis and decompensated cirrhosis, respectively. Conclusion: Compared to compensated cirrhosis patients, decompensated cirrhosis patients had higher costs, especially for hospitalization, injection, examination, and drugs administrated within medical institutions.